346 research outputs found
A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia
International audienceRelevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2R gamma(null)(c) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies
[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography
Purpose 111In (typically as [111In]oxinate3) is a gold standard
radiolabel for cell tracking in humans by scintigraphy. A long
half-life positron-emitting radiolabel to serve the same purpose
using positron emission tomography (PET) has long
been sought. We aimed to develop an 89Zr PET tracer for cell
labelling and compare it with [111In]oxinate3 single photon
emission computed tomography (SPECT).
Methods [89Zr]Oxinate4 was synthesised and its uptake and
efflux were measured in vitro in three cell lines and in human
leukocytes. The in vivo biodistribution of eGFP-5T33 murine
myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3
was monitored for up to 14 days. 89Zr retention by living
radiolabelled eGFP-positive cells in vivo was monitored by
FACS sorting of liver, spleen and bone marrow cells followed
by gamma counting.
Results Zr labelling was effective in all cell types with yields
comparable with 111In labelling. Retention of 89Zr in cells
in vitro after 24 h was significantly better (range 71 to
>90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo
showed the same early biodistribution whether labelled with
111In or 89Zr (initial pulmonary accumulation followed by
migration to liver, spleen and bone marrow), but later translocation
of radioactivity to kidneys was much greater for 111In.
In liver, spleen and bone marrow at least 92 % of 89Zr
remained associated with eGFP-positive cells after 7 days
in vivo.
Conclusion [89Zr]Oxinate4 offers a potential solution to the
emerging need for a long half-life PET tracer for cell tracking
in vivo and deserves further evaluation of its effects on survival
and behaviour of different cell types
A niche-like culture system allowing the maintenance of primary human acute myeloid leukemia-initiating cells: A new tool to decipher their chemoresistance and self-renewal mechanisms
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Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays
The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange
hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6
e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at
the PEP-II collider. The spectrum is used to measure the branching fraction B(B
--> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the
first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm
0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm
0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011
\pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the
photon energy in the B-meson rest frame. Results are also presented for
narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B -->
X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also
unfolded to the B-meson rest frame; that is the frame in which theoretical
predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No
analysis or results have changed from previous version. Some changes to
improve clarity based on interactions with Phys. Rev. D referees, including
one new Figure (Fig. 13), and some minor wording/punctuation/spelling
mistakes fixe
Improved Limits on decays to invisible final states
We establish improved upper limits on branching fractions for B0 decays to
final States 10 where the decay products are purely invisible (i.e., no
observable final state particles) and for final states where the only visible
product is a photon. Within the Standard Model, these decays have branching
fractions that are below the current experimental sensitivity, but various
models of physics beyond the Standard Model predict significant contributions
for these channels. Using 471 million BB pairs collected at the Y(4S) resonance
by the BABAR experiment at the PEP-II e+e- storage ring at the SLAC National
Accelerator Laboratory, we establish upper limits at the 90% confidence level
of 2.4x10^-5 for the branching fraction of B0-->Invisible and 1.7x10^-5 for the
branching fraction of B0-->Invisible+gammaComment: 8 pages, 3 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
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Precise Measurement of the e+ e- --> pi+ pi- (gamma) Cross Section with the Initial-State Radiation Method at BABAR
A precise measurement of the cross section of the process
from threshold to an energy of 3GeV is obtained
with the initial-state radiation (ISR) method using 232fb of data
collected with the BaBar detector at center-of-mass energies near
10.6GeV. The ISR luminosity is determined from a study of the leptonic process
, which is found to agree with the
next-to-leading-order QED prediction to within 1.1%. The cross section for the
process is obtained with a systematic uncertainty
of 0.5% in the dominant resonance region. The leading-order hadronic
contribution to the muon magnetic anomaly calculated using the measured
cross section from threshold to 1.8GeV is .Comment: 58 pages, 56 figures, to be submitted to Phys. Rev.
Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-
In a sample of 471 million BB events collected with the BABAR detector at the
PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is
either e+e- or mu+mu-. We report results on partial branching fractions and
isospin asymmetries in seven bins of di-lepton mass-squared. We further present
CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi
resonance. We find no evidence for CP or lepton-flavor violation. The partial
branching fractions and isospin asymmetries are consistent with the Standard
Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.
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Measurement of the Time-Dependent CP Asymmetry of Partially Reconstructed B0->D*+D*- Decays
We present a new measurement of the time-dependent CP asymmetry of B0->D*+D*-
decays using (471+-5) million BBbar pairs collected with the BaBar detector at
the PEP-II B Factory at the SLAC National Accelerator Laboratory. Using the
technique of partial reconstruction, we measure the time-dependent CP asymmetry
parameters S=-0.34+-0.12+-0.05$ and C=+0.15+-0.09+-0.04. Using the value for
the CP-odd fraction R_perp=0.158+-0.028+-0.006, previously measured by BaBar
with fully reconstructed B0->D*+D*- events, we extract the CP-even components
S+=-0.49+-0.18+-0.07+-0.04 and C+=+0.15+-0.09+-0.04. In each case, the first
uncertainty is statistical and the second is systematic; the third uncertainty
on S+ is the contribution from the uncertainty on R_perp. The measured value of
the CP-even component S+ is consistent with the value of sin(2Beta) measured in
b->(ccbar)s transitions, and with the Standard Model expectation of small
penguin contributions.Comment: 17 pages, 7 figures, submitted to Physical Review
Measurement of CP Asymmetries and Branching Fractions in Charmless Two-Body B-Meson Decays to Pions and Kaons
We present improved measurements of CP-violation parameters in the decays
, , and , and of
the branching fractions for and . The
results are obtained with the full data set collected at the
resonance by the BABAR experiment at the PEP-II asymmetric-energy factory
at the SLAC National Accelerator Laboratory, corresponding to
million pairs. We find the CP-violation parameter values and
branching fractions where in each case, the first uncertainties are statistical
and the second are systematic. We observe CP violation with a significance of
6.7 standard deviations for and 6.1 standard deviations for
, including systematic uncertainties. Constraints on the
Unitarity Triangle angle are determined from the isospin relations
among the rates and asymmetries. Considering only the solution
preferred by the Standard Model, we find to be in the range
at the 68% confidence level.Comment: 18 pages, 11 postscript figures, submitted to Phys. Rev.
Search for lepton-number violating processes in B+ -> h- l+ l+ decays
We have searched for the lepton-number violating processes B+ -> h- l+ l+
with h- = K-/pi- and l+ = e+/mu+, using a sample of 471+/-3 million BBbar
events collected with the BaBar detector at the PEP-II e+e- collider at the
SLAC National Accelerator Laboratory. We find no evidence for these decays and
place 90% confidence level upper limits on their branching fractions Br(B+ ->
pi- e+ e+) K- e+ e+) pi-
mu+ mu+) K- mu+ mu+) < 6.7 x 10^{-8}.Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D. R
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